Summary We believe that our project is responsive to the HLS16-02 Small Business Topic of Special Interest for NHLBI Fiscal Year 2016. Here, we will develop commercialization-ready advanced functional imager to assess red blood cell (RBC) transfusion. We successfully finished Phase I by developing the device?s prototype and testing its functionality in the proof-of-principle experiments in scattering phantom and two dorsal window mice models. In Phase II of the project the device will be verified with established functional microscopy in the dorsal window animal model, next the RBC transfusion microcirculation endpoint markers will be correlated with established organ wellness markers in the cranial window mouse model and finally the design and software of the clinically-ready imager will be finalized in a small study of volunteers. The key features of the imager are the ability to quantify local microcirculation parameters including tissue oxygen supply and consumption with a handheld probe for easy tissue access. Our market research and analysis indicates a strong demand for such instrument to help physicians effectively perform RBC transfusion, which is the most common inpatient hospital procedure. We estimate that our device can save annually up to $300 million in health care costs in the US. Currently there are no defined markers of the RBC transfusion efficiency evaluation, except the hemoglobin and hematocrit level, which do not address function. Conventional optimization of macrocirculatory (arterial blood pressure, cardiac output etc.) and tissue perfusion (acidosis, lactate, venous O2 saturation (SvO2), organ function etc.) parameters do not demonstrate beneficial results. We hypothesize that the microcirculation, including capillary density, blood oxygenation, flow and oxygen extraction in arterioles and venules with diameters of 20-100 m, can provide crucial endpoints for optimization of the RBC transfusion. To reduce the risk of infection or injury in vulnerable patients and to minimize number of blood draws, a non-invasive microcirculation assessment, if validated, would be highly preferred over invasive or minimally invasive methods. We believe our approach provides the needed performance to solve a critical problem and a clear path to successful commercialization. This project will have strong social impact by providing crucial clinical information to improve patient outcomes. Quantitative imaging of local tissue oxygen delivery and consumption will not only improve outcomes with RBC transfusion but has great potential to decrease morbidity and mortality in many devastating diseases with vascular etiology including a variety of malignant, inflammatory, ischemic, infectious and immune disorders.